Cyclin A1 is highly expressed in testis and acute myeloid leukemia where it is involved in male meiosis and cell cycle regulation at the restriction points G1/S and G2/M. Generally, cyclin A1 expression levels are low in most somatic cells 
. Here we show that cyclin A1 is also expressed in skeletal muscle cells lines and muscle tissue but significantly higher in FSHD patients vs. healthy controls at both RNA and protein level.
Interestingly, both cyclin A1 and DUX4 are classified to be epigenetically repressed in somatic cells, and DUX4-fl (a full-length open reading frame mRNA) is known to be a germline transcription factor specifically expressed in FSHD muscle cell lines and muscle tissue contributing to FSHD pathophysiology 
. In contrast to that, Jones et al. 
found DUX4-fl expressed at mRNA and protein level in up to 50% of muscle cells and biopsies derived from non-FSHD individuals meaning that it is not sufficient to induce muscle pathology in FSHD.
In FSHD, many genes downstream to DUX4 are activated. There are two transcripts of DUX4, the already mentioned DUX4-fl and DUX4-s, an internally spliced form of DUX4 mRNA. CCNA1
is downstream to both DUX4-fl and DUX4-s and its expression is obviously 3-fold or even more increased in FSHD patients vs. healthy controls 
. Recently, it has been reported that cyclin A1 is also up-regulated at RNA level in human immortalized contracted FSHD vs. non-contracted cells 
. Therefore, our data confirm these findings.
Due to the fact that cyclin A1 is a DUX4-induced protein its inappropriate activation may enter cell cycle processes in the post-mitotic muscle tissue. Interestingly, other highly differentiated post-mitotic cells, for example adult central nervous system neurons, keep their cell cycle in check and re-initiate it at the risk of neurodegeneration 
. We think a similar process might occur in dystrophic muscle which could indicate a putative role of cyclin A1 in the regeneration processes. Elevated cyclin A1 levels lead to chromatin condensation and apoptosis in renal, ovarian and lung carcinoma cells 
. Therefore, cyclin A1 could be involved in a way that it controls chromatin de-condensation present in both FSHD-1 and FSHD-2. However, a role of cyclin A1 as a hypothetical protein involved in chromatin formation leaves a question mark and needs to be determined in the future. Furthermore, apoptosis in FSHD occurs at a very low level and cyclin A1 does not seem to play a crucial role here 
FSHD primary cell lines are heterogeneous and often contaminated with fibroblasts. In human embryonic fibroblasts, cyclin A1 is highly expressed but redundant 
. Therefore, we studied CCNA1
expression in muscle tissue cultures of FSHD and control subjects and found comparable results at the RNA level. In our microarray assays, CCNA1
expression was detectable at very low levels in healthy controls as well as in some other myopathies such as CAV3, DYSF and FHL1. We could confirm these data in all FSHD patients and healthy controls by RT-PCR analyses. Even if CCNA1
was detectable at very low levels it was still significantly up-regulated in FSHD patients vs. healthy controls. Interestingly, during myotubes formation, percentage of fibroblast decreased (our own observation) leading finally to an almost pure, high-quality culture of differentiated cells (myotubes). Furthermore, results from RT-PCR, where total RNA was isolated from fresh tissue biopsy, confirmed tissue culture experiment. Nevertheless, cyclin A1 is known to be expressed in hematopoietic progenitor cells and we cannot exclude that its increased expression in our study derives from these cells within our biopsy samples 
Progression of FSHD along different muscles shows considerable differences and is obviously patient-specific. In our study, the site of muscle biopsy was chosen for clinical reasons and usually mildly weak muscles (grade 4– affected muscles of the 0–5 Medical Research Council Scale 
) were biopsied. Still, the material used in this study was heterogeneous. Differences between FSHD cell lines refer to different time points of myoblast growth, expansion and myotube formation in tissue culture, well-known among those working on FSHD. RNA expression levels of cyclin A1 were almost similar in FSHD myoblasts and myotubes within the same patient. Nevertheless, we observed large individual differences of CCNA1 mRNA expression between myoblasts and myotubes and also a large variability of Ct values in myoblasts in both FSHD and control cell lines. This could be due to culturing conditions commonly known in FSHD or, alternatively, an individual variability among subjects as reported by Homma et al. 
Results corresponding to the increased muscle myofiber diameter in FSHD are ambiguous. In animal models, muscle hypertrophy was reported and referred mainly to the increase in muscle protein mass. In patients, pseudo-hypertrophy was reported and attributed mainly to deposition of fat and connective tissue 
. We did not observe significant changes in IGF-1 RNA levels (data not shown) in the whole group but we found significantly (p<
0.001) increased muscle fiber diameters in FSHD-1 patients vs. healthy controls. Magnetic resonance images could help us to exclude/include the presence of fat and connective tissue infiltration resulting in pseudo-hypertrophy. From our data, we can only speculate that myofiber diameter increases in non-affected muscles to compensate for atrophy of affected muscles in FSHD patients.
Taken together, increased cyclin A1 protein expression could correspond to the increase in muscle protein mass, indicating, for example, disturbances in protein turnover finally leading to muscle hypertrophy 
. The relation between cell cycle disruption and hypertrophy has not yet been shown in FSHD. Interestingly, one of the ways to counteract excessive cell cycle activation is entering the process of apoptosis 
. Therefore, the relation between cell cycle activation, hypertrophy and apoptosis as processes controlling protein mass should be addressed in future studies.